Abstract: AIM:This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate(GLN) on the pharmacokinetics of entecavir(ETV) in rats.METHODS:Male SD rats were randomized into short-term and long-term experimental groups,respectively.In the short-term experiment,the control group received saline,the low dose group received GLN 13.5 mg·kg-1 and the high dose group received GLN 40.5 mg·kg-1.ETV(0.09 mg·kg-1) was given i.g.0.5 h after saline/GLN administration.For the long-term experiment,rats were allocated into two experimental designs.The control group received saline/ETV(0.09 mg·kg-1),the low dose group received GLN 13.5 mg·kg-1/ETV 0.09 mg·kg-1+GLN 13.5 mg·kg-1,while the high dose group received GLN 40.5 mg·kg-1/ETV 0.09 mg·kg-1+GLN 40.5 mg·kg-1;all administration was continued for 15 days.On the 16th day,0.09 mg·kg-1 ETV was administrated to all groups.Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations.RESULTS:Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments.CONCLUSIONS:Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats.